The research program continues to be a study of synaptic mechanisms that operate in the outer synaptic layer of the vertebrate retina. Projects will be continued on calcium-dependent transmitter release, carrier- mediated transmitter release, and the modulation of electrical transmission. Projects related to synaptic transmission are: 1. Compare the voltage dependence of the calcium current in photoreceptors with the voltage dependence of exocytosis. 2. Determine the spatial distribution for calcium entry into a photoreceptor inner segment during depolarization. 3. Determine the Ca-dependence and voltage-dependence for the transfer of information in each direction across the reciprocal synapse between a cone and a horizontal cell. 4. Determine the Ca- dependence for the transfer of information at basal synapses between adjacent cones. 5. Determine the Ca-dependence and voltage-dependence for the transfer of information at basal synapses between cones and bipolar cells. 6. Characterize the modulation by cyclic AMP and cyclic GMP of gap junction channels that connect horizontal cells. In addition, the technology for optically imaging the activity of many cells simultaneously will be developed. 7. The pathway of activity from a photoreceptor to the ganglion cells will be compared for a stimulus that begins in a rod or in a cone. Cellular activity will be imaged with dyes sensitive to intracellular ion concentrations and membrane voltage using a confocal microscope and digital image processing.